Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The sequence and resolved structure of thermotrophic isopropylmalate dehydrogenase (IPMDH) and a related protein, mesotrophic isocitrate dehydrogenase (IDH), were compared emphasizing clusters of charged residues identified from X-ray crystallographic studies (Wallon, G., Kryger, G., Lovett, S. T., Oshima, T., Ringe, D., and Petsko, G. A. (1997) J. Mol. Biol. 266, 1016-1031). Mesotrophic isocitrate dehydrogenase was used for comparison because crystallographic data for a mesotrophic form of IPMDH was not available in the database. The structural features in the region of these clusters were compared and localized conformational differences were found in the thermotroph compared to the mesotroph. Because the overall topology of the two proteins is similar, it was concluded that these localized structural differences induced by electrostatic interactions between charged residues in the thermotrophic enzyme were responsible for the enhanced thermal stability of proteins from thermotroph.
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PMID:Localized structural effects of electrostatic interactions in a thermostable enzyme. 1022 56

Oxidative damage, through increased production of free radicals, is believed to be involved in UV-induced cataractogenesis (eye lens opacification). The possibility of UVB radiation causing damage to important lenticular enzymes was assessed by irradiating 3 months old rat lenses (in RPMI-1640 medium) at 300 nm (100 microWcm(-2)) for 24 h, in the absence and presence of ascorbic acid, alpha-tocopherol acetate and beta-carotene. UVB irradiation resulted in decreased activities of hexokinase, glucose-6-phosphate dehydrogenase, aldose reductase, and Na, K- ATPase by 42, 40, 44 and 57% respectively. While endopeptidase activity (229%) and lipid peroxidation (156%) were increased, isocitrate dehydrogenase activity was not altered on irradiation. In the presence of externally added ascorbic acid, tocopherol and beta-carotene (separately) to the medium, the changes in enzyme activities (except endopeptidase) and increased lipid peroxidation, due to UVB exposure, were prevented. These results suggest that UVB radiation exerts oxidative damage on lens enzymes and antioxidants were protective against this damage.
Mol Cell Biochem 1999 Apr
PMID:Protection against UVB inactivation (in vitro) of rat lens enzymes by natural antioxidants. 1039 Nov 22

Isocitrate dehydrogenase catalyses the two step, acid base, oxidative decarboxylation of isocitrate to alpha-ketoglutarate. Lysine 230 was suggested to act as proton donor based on geometry and spatial proximity to isocitrate. To clarify further the role of lysine 230, we co-crystallized the lysine-to-methionine mutant (K230M) with isocitrate and with alpha-ketoglutarate. Crystals were flash-frozen and the two structures were determined and refined to 2. 1 A. Several new features were identified relative to the wild-type structure. Seven side-chains previously unplaced in the wild-type structure were identified and included in the model, and the amino acid terminus was extended by an alanine residue. Many additional water molecules were identified. Examination of the K230M active sites (K230M isocitrate and K230M-ketoglutarate) revealed that tyrosine 160 protrudes further into the active site in the presence of either isocitrate or alpha-ketoglutarate in K230 M than it does in the wild-type structure. Also, methionine 230 was not as fully extended, and asparagine 232 rotates approximately 30 degrees toward the ligand permitting polar interactions. Outside the active site cleft a tetragonal volume of density was identified as a sulfate molecule. Its location and interactions suggest it may influence the equilibrium between the tetragonal and the orthorhombic forms of isocitrate dehydrogenase. Differences observed in the active site water structure between the wild-type and K230M structures were due to a single point mutation. A water molecule was located in the position equivalent to that occupied by the wild-type epsilon-amine of lysine 230; a water molecule in that location in K230M suggests it may influence catalysis in the mutant. Comparison of K230M complexed with isocitrate and alpha-ketoglutarate illuminates the influence a ligand has on active site water structure.
J Mol Biol 2000 Jan 21
PMID:Active site water molecules revealed in the 2.1 A resolution structure of a site-directed mutant of isocitrate dehydrogenase. 1062 32

Prolactin (PRL) has an important role in the regulation of water and electrolyte homeostasis in teleosts. The present study was designed to evaluate the role of PRL and GH on malic enzyme (ME), glucose-6-phosphate dehydrogenase (G6PDH) and isocitrate dehydrogenase (ICDH) in Anabas testudineus. Ovine prolactin significantly inhibited ME, G6PDH and ICDH activities when administered in vivo compared to vehicle treated controls. In vivo administration of PRL reversed the action of bromocryptine on enzyme activities. Ovine growth hormone in vivo also modified the effect of bromocryptine but not to the level of prolactin. Combined action of PRL+GH in vivo was most effective in keeping the enzyme activities at normal level after bromocryptine treatment. Prolactin in vitro also reversed the action of bromocryptine on enzyme activities, while GH in vitro failed to do so. Hence, prolactin seems to have an inhibitory effect on lipid metabolism in this teleost. Combined action of PRL+GH is more prominent in in vivo conditions at low PRL levels. Dopaminergic pathways may be involved in the control of prolactin and to some extent on growth hormone secretion.
Comp Biochem Physiol B Biochem Mol Biol 2001 Apr
PMID:In vivo and in vitro effects of prolactin and growth hormone on lipid metabolism in a teleost, Anabas testudineus (Bloch). 1129 Apr 58

The production of reactive oxygen species (ROS), such as O2- and H2O2, is an unavoidable consequence of aerobic metabolism. In plant cells the mitochondrial electron transport chain (ETC) is a major site of ROS production. In addition to complexes I-IV, the plant mitochondrial ETC contains a non-proton-pumping alternative oxidase as well as two rotenone-insensitive, non-proton-pumping NAD(P)H dehydrogenases on each side of the inner membrane: NDex on the outer surface and NDin on the inner surface. Because of their dependence on Ca2+, the two NDex may be active only when the plant cell is stressed. Complex I is the main enzyme oxidizing NADH under normal conditions and is also a major site of ROS production, together with complex III. The alternative oxidase and possibly NDin(NADH) function to limit mitochondrial ROS production by keeping the ETC relatively oxidized. Several enzymes are found in the matrix that, together with small antioxidants such as glutathione, help remove ROS. The antioxidants are kept in a reduced state by matrix NADPH produced by NADP-isocitrate dehydrogenase and non-proton-pumping transhydrogenase activities. When these defenses are overwhelmed, as occurs during both biotic and abiotic stress, the mitochondria are damaged by oxidative stress.
Annu Rev Plant Physiol Plant Mol Biol 2001 Jun
PMID:PLANT MITOCHONDRIA AND OXIDATIVE STRESS: Electron Transport, NADPH Turnover, and Metabolism of Reactive Oxygen Species. 1133 9

The capacity of white adipose tissue mitochondria to support a high beta-oxidative flux was investigated by comparison to liver mitochondria. Based on marker enzyme activities and electron microscopy, the relative purity of the isolated mitochondria was similar thus allowing a direct comparison on a protein basis. The results confirm the comparable capacity of adipose tissue and liver mitochondria for palmitoyl-carnitine oxidation. Relative to liver, both citrate synthase and alpha-ketoglutarate dehydrogenase were increased 7.87- and 10.38-fold, respectively. In contrast, adipose tissue NAD-isocitrate dehydrogenase was decreased (2.85-fold). Such modifications in the citric acid cycle are expected to severely restrict citrate oxidation in porcine adipose tissue. Except for cytochrome c oxidase, activities of the enzyme complexes comprising the electron transport chain were not significantly different. The decrease in adipose cytochrome c oxidase activity could partly be attributed to a decreased inner membrane as suggested by lipid and enzyme analysis. In addition, Western blotting indicated that adipose and liver mitochondria possess similar quantities of cytochrome c oxidase protein. Taken together these results indicate that not only is the white adipose tissue protoplasm relatively rich in mitochondria, but that these mitochondria contain comparable enzymatic machinery to support a relatively high beta-oxidative rate.
Comp Biochem Physiol B Biochem Mol Biol 2001 Jul
PMID:Biochemical properties of porcine white adipose tissue mitochondria and relevance to fatty acid oxidation. 1143 34

Few data are available on enzyme activity in amphibian plasma or erythrocytes. We measured the activity of several blood enzymes in the urodele amphibian Pleurodeles waltl reared under standard laboratory conditions. In subsequent experiments, we will estimate and compare the physiological and biochemical conditions of P. waltl when reared under extreme temperature or microgravity conditions. The enzymes selected were glutamate dehydrogenase, aspartate aminotransferase, alanine aminotransferase, superoxide dismutase, catalase, isocitrate dehydrogenase and glucose-6-phosphate dehydrogenase. In fresh plasma samples, enzyme activity in females was higher than in males, except for aspartate and alanine aminotransferases, which were equivalent in females and males. Glutamate dehydrogenase activity was higher in males than in females. In female erythrocytes, the activity of all enzymes was higher than in male erythrocytes. We have also studied the storage conditions of samples and observed that for most enzymes, the activity in freshly isolated plasma and erythrocyte preparations decreased after storage at -18 or +4 degrees C.
Comp Biochem Physiol A Mol Integr Physiol 2001 Nov
PMID:Sex-linked differences in activity of enzymes in the blood of the urodele amphibian Pleurodeles waltl. 1169 17

Rapid action of steroid hormones on lipid metabolism is not reported so far in any vertebrate. The present study was intended to evaluate the quick actions of cortisol and testosterone on enzymes, namely malic enzyme (ME), glucose-6-phosphate dehydrogenase (G6PDH), and isocitrate dehydrogenase (ICDH) in Oreochromis mossambicus. Cortisol and testosterone produced rapid and opposite effects on the lipogenic enzymes studied. Cortisol significantly decreased the activities of ME, G6PDH, as early as 5 min and ICDH as early as 10 min in vitro (10(-6) M), and 30 min in vivo (0.1 microg/g body wt.) whereas the same doses of testosterone significantly stimulated the activity of all enzymes as early as 5 min in vitro and 30 min in vivo. Actinomycin D treatment did not interfere with the inhibiting effect of cortisol on enzyme activities when measured at 10 min in the in vitro system. The transcriptional inhibitor appeared to partially block the effect of cortisol in vivo. The stimulatory effect of testosterone was insensitive to the action of actinomycin D both in vivo and in vitro. These effects appear to be brought about independently of new protein synthesis because the rapid responses occurred within a latent period of 5-30 min and were insensitive to the action of actinomycin D, suggesting a non-genomic action.
Comp Biochem Physiol B Biochem Mol Biol 2002 Mar
PMID:Rapid action of cortisol and testosterone on lipogenic enzymes in a fresh water fish Oreochromis mossambicus: short-term in vivo and in vitro study. 1195 13

Trypanosoma brucei procyclic trypomastigotes and T. cruzi epimastigotes (both Tulahuen and Y strains) were permeabilized by incubation with increasing amounts of digitonin, causing enzymes to be released from different intracellular compartments. After 10 min incubation with digitonin, the cells were centrifuged and the activity of marker enzymes (aspartate-dependent malic enzyme for cytoplasm, hexokinase for glycosomes and either isocitrate dehydrogenase or citrate synthase for mitochondria) was analyzed in the supernatant. The results were compared with the release of NADH-fumarate reductase in order to determine if this enzyme was preferentially released with a specific intracellular marker. Fumarate reductase was released at lower digitonin concentration than those required to either release isocitrate dehydrogenase or citrate synthase. Similarly, Leishmania donovani promastigotes (S-2 strain) were exposed to a single concentration of digitonin (200 micro M) but in this case we monitored the release of fumarate reductase and hexokinase, while monitoring the mitochondrial membrane potential (using safranine O). Again, substantial fumarate reductase and hexokinase activities were released without loss of mitochondrial membrane potential indicating that part of the enzyme was released while the inner mitochondrial membrane remained intact. These results suggest that, in the three species of trypanosomatids the enzyme fumarate reductase is, at least in part, located outside the mitochondrial matrix.
Comp Biochem Physiol B Biochem Mol Biol 2002 Sep
PMID:Extramitochondrial localization of NADH-fumarate reductase in trypanosomatids. 1222 8

To understand the many roles of the Krebs tricarboxylic acid (TCA) cycle in cell function, we used DNA microarrays to examine gene expression in response to TCA cycle dysfunction. mRNA was analyzed from yeast strains harboring defects in each of 15 genes that encode subunits of the eight TCA cycle enzymes. The expression of >400 genes changed at least threefold in response to TCA cycle dysfunction. Many genes displayed a common response to TCA cycle dysfunction indicative of a shift away from oxidative metabolism. Another set of genes displayed a pairwise, alternating pattern of expression in response to contiguous TCA cycle enzyme defects: expression was elevated in aconitase and isocitrate dehydrogenase mutants, diminished in alpha-ketoglutarate dehydrogenase and succinyl-CoA ligase mutants, elevated again in succinate dehydrogenase and fumarase mutants, and diminished again in malate dehydrogenase and citrate synthase mutants. This pattern correlated with previously defined TCA cycle growth-enhancing mutations and suggested a novel metabolic signaling pathway monitoring TCA cycle function. Expression of hypoxic/anaerobic genes was elevated in alpha-ketoglutarate dehydrogenase mutants, whereas expression of oxidative genes was diminished, consistent with a heme signaling defect caused by inadequate levels of the heme precursor, succinyl-CoA. These studies have revealed extensive responses to changes in TCA cycle function and have uncovered new and unexpected metabolic networks that are wired into the TCA cycle.
Mol Biol Cell 2003 Mar
PMID:Global transcription analysis of Krebs tricarboxylic acid cycle mutants reveals an alternating pattern of gene expression and effects on hypoxic and oxidative genes. 1263 16


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